Marijuana continues to be the most commonly used illicit drug in this country, with an estimated 12 million current users. This project is designed to study the behavioral effects of smoked marijuana and oral delta-9-tetrahydrocannabinol (THC) that are relevant to the abuse of this class of drugs. The subject population will be male and female human volunteers who are experienced cannabis users. The proposed studies utilize within-subject repeated-measures designs and methods which are extensions of those originally developed to study the behavioral effects of drugs of abuse in laboratory animals. Dependent measures common to most of the studies include subjective effects, heart rate and body sway. The aim of one study is to determine the effect of one parameter of smoking topography (depth of inhalation) on the behavioral and physiological response to marijuana. This issue is of clinical relevance because marijuana smoking is associated with pulmonary toxicity, and depth of inhalation could affect the location and extent of deposition of toxic smoke constituents in the respiratory tract. This study will also provide data on the relationship between expired air carbon monoxide, an easily obtained, noninvasive index of smoke absorption, and plasma THC level after marijuana smoking. Another study is designed to assess the duration of behavioral impairment that occurs after marijuana smoking, an issue of clear importance in terms of public safety. Two studies examine the role that classical conditioning plays in determining the subjective and physiological responses that occur when subjects smoke placebo marijuana. The remaining studies, which comprise the bulk of the application, deal with the discriminative stimulus and reinforcing effects of the cannabinoids. There has been considerable public concern about the availability of high-potency marijuana. Two studies examine the role of marijuana THC content (potency) on marijuana self- administration. One assesses subjects' preference for high- versus low-potency marijuana. The other addresses the issue of whether users make compensatory changes in their smoking behavior (titration) when smoking marijuana of different potencies. Two studies investigate the effect of alcohol on marijuana self-administration. These studies should provide valuable insights into the reinforcing effects of this common drug combination. Incorporated into the design of several of the studies are two additional factors which are believed to be important determinants of the behavioral effects of drugs of abuse: extent of previous use of the drug (drug history) and information provided to experimental subjects about the study (instructional set). Overall, the project should provide significant new information on the behavioral and pharmacological determinants of marijuana use.